Ciliary regulation of melanogenesis unveils moonlighting roles for Joubert Syndrome proteins
- 1Department of Pathology and Laboratory Medicine and Department of Physiology, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, U
Abstract
We previously found that skin tone correlates with intronic polymorphisms influencing the expression of the Joubert Syndrome (JS) ciliopathy gene TMEM138, suggesting that primary cilia might regulate pigment production in skin melanocytes. Herein, we show that many ciliary proteins regulate basal pigmentation in wild-type mouse and human melanocytes by facilitating primary cilium-dependent Melanocortin-1 receptor signaling, and downstream activation of the Microphthalmia transcription factor and melanogenic gene expression. Additionally, we identify an extra-ciliary moonlighting role for TMEM138 and other JS proteins in endolysosomal organization required for the biogenesis of melanosomes, the pigment-producing lysosome-related organelle in melanocytes. Our results provide new mechanistic insights into the physiological regulation of pigmentation and suggest that JS-specific pathology might be mediated by ciliary-independent mechanisms.
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BibTeX
@misc{magne2026ciliary,
title = {{Ciliary regulation of melanogenesis unveils moonlighting roles for Joubert Syndrome proteins}},
author = {B. Magne and S. Forsey and D. C. Harper and J. Zhang and C. E. Snider and Y. Feng and S. A. Tishkoff and A. Strong and T. G. Drivas and C. R. Goding and R. J. Lee and M. S. Marks},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.27.754807},
url = {https://www.biorxiv.org/content/10.64898/2026.09.27.754807v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Ciliary regulation of melanogenesis unveils moonlighting roles for Joubert Syndrome proteins
AU - B. Magne
AU - S. Forsey
AU - D. C. Harper
AU - J. Zhang
AU - C. E. Snider
AU - Y. Feng
AU - S. A. Tishkoff
AU - A. Strong
AU - T. G. Drivas
AU - C. R. Goding
AU - R. J. Lee
AU - M. S. Marks
PY - 2026
DA - 2026/09/27
PB - bioRxiv
DO - 10.64898/2026.09.27.754807
UR - https://www.biorxiv.org/content/10.64898/2026.09.27.754807v1
AB - We previously found that skin tone correlates with intronic polymorphisms influencing the expression of the Joubert Syndrome (JS) ciliopathy gene TMEM138, suggesting that primary cilia might regulate pigment production in skin melanocytes. Herein, we show that many ciliary proteins regulate basal pigmentation in wild-type mouse and human melanocytes by facilitating primary cilium-dependent Melanocortin-1 receptor signaling, and downstream activation of the Microphthalmia transcription factor and melanogenic gene expression. Additionally, we identify an extra-ciliary moonlighting role for TMEM138 and other JS proteins in endolysosomal organization required for the biogenesis of melanosomes, the pigment-producing lysosome-related organelle in melanocytes. Our results provide new mechanistic insights into the physiological regulation of pigmentation and suggest that JS-specific pathology might be mediated by ciliary-independent mechanisms.
ER -